How hormone therapy works

Oestrogen and progesterone are hormones which are naturally produced in the human body. Before menopause, oestrogen is mostly produced by the ovaries. After menopause, when the ovaries are no longer active a small amount continues to be produced in other tissues such as fat, muscle and adrenal glands.

Normal breast cells contain receptors (proteins) which are able to recognise these hormones and allow them to access the cells. Once inside the cells the hormones release signals which encourage growth and development. All breast cancers are tested for the presence of these oestrogen and progesterone receptors, using tissue taken at the time of biopsy or surgery. Approximately 70% of breast cancers retain these receptors, and rely on these hormones (particularly oestrogen) to grow. These hormone-sensitive cancers are known as oestrogen receptor positive (ER+) and/or progesterone receptor positive (PR+).

By blocking the production of oestrogen, or preventing it from stimulating breast cancer cells, hormone therapy minimises the cancer cells’ exposure to oestrogen and is given to prevent the breast cancer recurring in the future. It also reduces the risk of developing a second breast cancer.

Hormone therapy is also used to reduce the growth of a breast cancer when surgery is not appropriate and to help shrink advanced stage (secondary or metastatic) breast cancers or slow their growth.

This therapy is only effective in hormone receptor- positive breast cancer and does not work in receptor- negative disease.

Hormone therapy for breast cancer is not the same as HRT (hormone replacement therapy). HRT raises the level of oestrogen +/- progesterone in the body and is not used in the treatment of breast cancer

Types of hormone therapy

There are 3 types of hormone therapy commonly used to treat early breast cancer:

We know that around half of all women prescribed these drugs eventually stop taking them because of the side-effects.

That's a lot of women missing out on the survival benefits that these treatments offer.

Chanda Warren, a breast cancer patient, Dr David Porter and Dr Helen Roberts join us to discuss these side-effects, the remedies for them, and what strategies you can use so that you can live a normal life while taking them.

Tamoxifen

Tamoxifen belongs to a group of drugs known as SERMS (Selective oEstrogen Receptor Modulators) which block the effect of oestrogen on breast cancer cells but allow some oestrogen to nourish other sites (for example, bones and uterus). It’s an “anti-oestrogen” agent which binds to the receptors and prevents oestrogen from entering the cancer cells. This reduces the risk of the cancer coming back in the future and helps prevent breast cancer-related deaths. It also reduces the chance of developing a second breast cancer.

Tamoxifen is the standard hormone therapy for pre-menopausal women with hormone receptor positive breast cancer but can also be given to post-menopausal women and to men. It’s taken once daily in tablet form.

You may be prescribed tamoxifen for 5-10 years depending on your risk of cancer recurrence, and the benefits of tamoxifen continue long after you stop taking it. Discuss the risks versus benefits in your case with your breast cancer specialist.

Post-menopausal women may sometimes be recommended to switch to an aromatase inhibitor after taking tamoxifen for 2-3 years. Tamoxifen may also be given in conjunction with Zoladex, another medication which switches off ovarian function in pre-menopausal women.

Tamoxifen has also been shown to reduce the risk of developing breast cancer in women who are at high risk of the disease.

If tamoxifen has been prescribed for you, download the patient information sheet:

Aromatase Inhibitors

After menopause, the ovaries stop making oestrogen, but small amounts continue to be produced from the adrenal glands and in fat and other peripheral tissue. An enzyme known as aromatase enables this process by changing other hormones to oestrogen. By blocking the aromatase enzyme and stopping this oestrogen production, aromatase inhibitors reduce the risk of the cancer coming back in the future and help prevent breast cancer-related deaths. They also lower the risk of a second breast cancer developing.

Aromatase inhibitors reduce the amount of oestrogen being produced in the body. They are mostly given to postmenopausal women whose ovaries no longer produce oestrogen. However, some pre-menopausal women who are at high risk of recurrence may be prescribed an aromatase inhibitor along with an injection (Zoladex) which stops the ovaries producing oestrogen. In early breast cancer treatment aromatase inhibitors are usually given only to women as there is limited data about their efficacy in men.

The benefits of taking A.I.s for a longer duration ( as with tamoxifen) have not been confirmed plus there would be a higher risk of bone related side effects. The benefit would be greatest for those at the highest risk of recurrence.

If an aromatase inhibitor has been prescribed for you, download the patient information sheet:

Ovarian suppression

Shutting down the ovaries so that they no longer produce oestrogen can reduce the risk of recurrence in pre-menopausal women with higher risk oestrogen receptor positive cancer.

This can be achieved with drug therapy, surgery or less commonly with irradiation.

Drug therapies

Luteinising hormone blockers GnRH/LHRH agonists

These agents signal the pituitary gland to stop producing luteinising hormone which is responsible for stimulating the production of oestrogen from the ovaries in pre-menopausal women.

Zoladex (goserelin)

Zoladex is delivered as a small implant which is given by injection under the skin (usually on the abdomen) every 28 days or alternatively at 3-monthly intervals. By shutting down the production of oestrogen, the treatment aims to prevent the growth of receptor positive breast cancer. It is used to lower the risk of recurrence after surgery and is usually given for two years in this situation. Zoladex can be used alone or in combination with tamoxifen or aromatase inhibitors. When used to shrink and control metastatic (secondary) breast cancer the treatment is continued for as long as it is being effective.

In young women, the ovarian function should recover after treatment ceases (unless you are close to the age of a natural menopause in which case the treatment might induce early menopause).

Oopherectomy – Surgical removal of the ovaries

Permanent and immediate suppression of ovarian function is achieved by surgically removing the ovaries (and usually the fallopian tubes). This can often be done via 3 small “keyhole” incisions in the abdomen, using a laparoscope (a flexible tube with an attached camera). If the laparoscopic method is not appropriate then the ovaries are removed through a short incision in the lower abdomen.

Removing the ovaries results in an immediate and permanent menopause as the production of oestrogen and progesterone from the ovaries is abruptly halted. The symptoms of a surgically induced menopause are usually more intense than those of a more gradual, natural menopause.

Side effects of hormone therapy

Some side effects are common to all methods of hormone therapy and are due to the reduced levels of oestrogen.

These include:

Hot flushes and sweats

Nausea

Vaginal dryness, itching

Lowered interest in sex

Fatigue

Mood changes

Tamoxifen and aromatase inhibitors also produce some different side effects. You may experience some of the side effects listed, but are unlikely to experience them all.

For most people who are recommended to take hormone therapy for breast cancer, the risks of treatment are outweighed by the benefits.

Here is a list of side effects that might be experienced on tamoxifen and aromatase inhibitors:

Tamoxifen

Aromatase Inhibitors

Common side effects

Hot flushes/night sweats

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Changes to periods

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Vaginal dryness, itchiness, irritation

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Vaginal discharge

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Reduced sex drive

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Fatigue

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Nausea

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Mood disturbance

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Joint and muscle pain

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Loss of bone density

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Less common side effects

Hair thinning

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Increased cholesterol levels

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Increased risk of heart disease

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Carpal tunnel syndrome

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Rare side effects

Blood clots (deep vein thrombosis, pulmonary embolism)

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Stroke

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Endometrial (uterine) cancer

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Cataracts

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Managing side effects

Many of the common side effects of hormonal therapy can be reduced or managed with the help and advice of your specialist breast cancer team.

Hot flushes

Regular exercise has been shown to reduce the frequency and intensity of hot flushes. Take note of anything which might trigger your hot flushes e.g. hot drinks, alcohol, spicy food, hot temperatures. Wear loose, natural fabrics (especially cotton) and dress in layers. It may be helpful to carry a small portable fan with you. If your hot flushes/night sweats are intolerable, talk to your doctor to see if you might be able to change medications or try some medication to reduce the flushes.

It is not advised to take herbal products such as Black Cohosh. These often contain phytoestrogens (plant oestrogens) and the safety of taking these supplements with hormone therapy for breast cancer has not been established.

Vaginal dryness or irritation

Lowered oestrogen levels cause the tissues of the vagina to become thin, dry and less elastic. The vagina becomes slightly shorter and narrower. (These changes also happen with menopause.)

Water-based lubricants such as Sylk can reduce the discomfort, particularly during sex. Vaginal moisturizers such as Replens (available online and from some pharmacies) help to hydrate the vaginal tissue and have a long lasting effect (up to 3 days at a time).

Vaginal discharge

A small amount of clear or white vaginal discharge is normal for many women but hormone therapy for breast cancer may cause an increase in the discharge volume. Wear loose, cotton underwear and panty liners if needed. Report any odour or discolouration such as blood to your doctor.

Nausea

This is quite common when starting hormonal therapy and often passes as your body learns to tolerate the drug. It may help to take the medication with food or at night before going to bed.

Bone and joint pain

It’s important to stay physically active to keep the muscles around your joints flexible. Regular exercise has been shown to reduce joint pain caused by hormone therapy.

Common mild analgesics such as paracetamol or some anti-inflammatories can also help, so talk to your doctor to see if these medications are appropriate for you. Hot packs may be soothing, yoga may be helpful and some people have gained relief with acupuncture.

Loss of bone density

If you have a strong family history of osteoporosis or a personal history of a fracture after a minor fall, talk to your doctor about having a DEXA scan to measure your bone density. Ensure you have a healthy diet incorporating adequate calcium.

Vitamin D also aids bone health and may be prescribed to you if you are taking an aromatase inhibitor.

Rare side effects

Deep vein thrombosis, pulmonary embolus and endometrial cancer are rare side effects of Tamoxifen. It’s important to urgently report any calf pain and swelling, shortness of breath or abnormal vaginal bleeding to your doctor.

Talk to your medical team

If you are experiencing any unpleasant side effects don’t suffer in silence. Talk with your breastcare/oncology nurse or doctor about any side effects you may be having. There may be ways to reduce the intensity of your symptoms or there may be alternative medications which suit you better.

Hormone therapy improves breast cancer outcomes, so your specialist team will support you in taking your medication as prescribed so that you will gain the maximum benefit.

fulvestrant ( Faslodex)

Fulvestrant is an oestrogen receptor down-regulator and can be used in oestrogen receptor positive,post menopausal, metastatic breast cancer. It can be used alone or in combination with palbociclib. It is given monthly by injection into the muscle.